Tumor invasiveness in human oral cancer is one of the most direct prognostic indicators of patient survival. Aberrant expression of the cell adhesion molecule N-cadherin has been correlated with increased invasiveness in both cell culture models and in human oral cancers. The long term goal underlying the proposed research is to define the role of N-cadherin in oral tumor progression. This proposal will examine the molecular mechanisms associated with N-cadherin mediated invasion in both cell culture and animal models of oral cancer. Oral squamous tumor cell lines that express either low or high levels of N-cadherin will be used to identify N-cadherin-mediated signaling pathways that contribute to the invasive phenotype. N-cadherin mutants will also be utilized to identify structural features of N-cadherin that modulate invasive signaling. A transgenic mouse that ectopically expresses N-cadherin in the oral epithelia has been developed and will be used to examine the role of N-cadherin on the invasiveness of chemically-induced oral tumors. This work will facilitate a better understanding of the mechanisms associated with oral tumor (progression, and may provide novel targets for the development of new treatment strategies for oral cancer. [unreadable] [unreadable] [unreadable]